VPS53 Inhibitors
Chemical inhibitors of VPS53 can impede its function in vesicle trafficking by various means, primarily through the disruption of vesicle formation, scission, and transport that are upstream of VPS53's role in the tethering and fusion of endosomes. Dynasore, MiTMAB, and Dyngo-4a are such inhibitors that target the GTPase activity of dynamin, essential in the endocytic pathway where vesicles are pinched off from the plasma membrane. Dynasore non-competitively inhibits dynamin, while MiTMAB blocks the dynamin's pleckstrin homology domain, and Iminodyn-17 is a small molecule that hinders the GTPase activity of dynamin. Dyngo-4a is a potent inhibitor of multiple dynamins, including dynamin-1, -2, and -3. These actions collectively result in the inhibition of vesicle scission, thereby preventing the formation of endocytic vesicles that VPS53 would normally process. Without these vesicles, VPS53 cannot perform its function in vesicle tethering and fusion, leading to a disruption in the endosome-to-Golgi transport.
Other inhibitors, such as Octylglucoside, Nocodazole, Cytochalasin D, Brefeldin A, and Monensin, affect VPS53 indirectly by altering the cellular components or environment necessary for vesicle transport and fusion. Octylglucoside, a nonionic detergent, disrupts lipid bilayers and can damage the vesicle membranes that VPS53 interacts with. Nocodazole, which depolymerizes microtubules, and Cytochalasin D, which disrupts actin filament polymerization, impede the structural integrity and movement of vesicles. Brefeldin A inhibits ADP-ribosylation factor, thus disrupting vesicle budding from the Golgi and, in turn, the availability of vesicles for VPS53 to process. Monensin alters ionic gradients across cellular membranes, particularly in the Golgi apparatus, affecting the maturation and trafficking of vesicles and indirectly inhibiting VPS53's tethering and fusion role. By compromising the formation, structure, and transport of vesicles, these inhibitors collectively contribute to the functional inhibition of VPS53 in the cell.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Dynamin Inhibitor I, Dynasore | 304448-55-3 | sc-202592 | 10 mg | $89.00 | 44 | |
Dynasore non-competitively inhibits the GTPase activity of dynamin, an essential component in the endocytic pathway, which VPS53 is also a part of. By inhibiting dynamin, Dynasore disrupts endosome trafficking. Since VPS53 is involved in the tethering and fusion of endosomes, Dynasore's action would result in functional inhibition of VPS53 by preventing proper endosome dynamics critical for its function. | ||||||
Hydroxy-Dynasore | 1256493-34-1 | sc-364678 | 10 mg | $255.00 | ||
Dyngo-4a is a potent inhibitor of dynamin-1, dynamin-2, and dynamin-3, which are large GTPases involved in the pinching off of clathrin-coated vesicles during endocytosis. Because VPS53 is involved in the subsequent trafficking of endocytic vesicles, Dyngo-4a's inhibition of dynamin activity indirectly inhibits VPS53 by halting the supply of vesicles that need to be tethered and fused at the Golgi, which is a process that requires VPS53. | ||||||
Nocodazole | 31430-18-9 | sc-3518B sc-3518 sc-3518C sc-3518A | 5 mg 10 mg 25 mg 50 mg | $59.00 $85.00 $143.00 $247.00 | 38 | |
Nocodazole is a microtubule-depolymerizing agent that disrupts microtubule dynamics. Microtubules are vital for vesicle transport in cells, and since VPS53 is involved in vesicle tethering and fusion, particularly in endosome-to-Golgi transport, the disruption of microtubules by Nocodazole would result in an indirect functional inhibition of VPS53 by preventing the microtubule-based transport of vesicles to their destination where VPS53-mediated tethering and fusion occur. | ||||||
Cytochalasin D | 22144-77-0 | sc-201442 sc-201442A | 1 mg 5 mg | $165.00 $486.00 | 64 | |
Cytochalasin D disrupts actin filament polymerization. Actin is known to play a role in maintaining vesicle structure and in vesicle movement. VPS53's function is dependent on vesicle transport and fusion, so the perturbation of actin dynamics by Cytochalasin D indirectly inhibits VPS53 by destabilizing the vesicles' structure and movement, thus impairing the protein's ability to mediate tethering and fusion of vesicles. | ||||||
Brefeldin A | 20350-15-6 | sc-200861C sc-200861 sc-200861A sc-200861B | 1 mg 5 mg 25 mg 100 mg | $31.00 $53.00 $124.00 $374.00 | 25 | |
Brefeldin A is a fungal metabolite that inhibits ADP-ribosylation factor (Arf), a small GTPase involved in vesicle budding from the Golgi. While VPS53 is engaged in endosome-to-Golgi transport, Brefeldin A's inhibition of Arf and subsequent disruption of vesicle formation from the Golgi can indirectly inhibit VPS53 by preventing the formation of vesicles that would require VPS53 for their processing. | ||||||
Monensin A | 17090-79-8 | sc-362032 sc-362032A | 5 mg 25 mg | $155.00 $525.00 | ||
Monensin acts as an ionophore that disrupts ionic gradients across cellular membranes, particularly in the Golgi apparatus. It alters intracellular pH and affects vesicle trafficking. Since VPS53 is involved in vesicle tethering and fusion in endosome-to-Golgi transport, the ionophoric action of Monensin could indirectly inhibit VPS53's function by altering the ionic environment necessary for vesicle maturation and trafficking, which are prerequisite steps for VPS53-mediated tethering and fusion processes. | ||||||